The aim of the present study was to assess the effect of calcium infusion on segmental tubular reabsorption in humans using lithium clearance, along with creatinine and free water clearances during maximal water diuresis. In 8 healthy volunteers, a 20-min 5 mg/kg calcium infusion that increased serum calcium levels from 2.27 ± 0.07 to 2.87 ± 0.07 mmol/l (p < 0.01) was followed by a 60-min 3 mg/kg infusion for maintenance. During the experimental period, blood pressure did not change. Maximal urine flow increased from 15.6 ± 2.4 to 20.8 ± 2.8 ml/min (p < 0.01), while clearance of sodium increased from 1.5 ± 0.4 to 3.7 ± 0.9 ml/min (p < 0.001). Lithium clearance showed an increase of 7.4 ml/min, pointing to a suppression of proximal reabsorption. Free water clearance also increased from 11.5 ± 3.7 to 14.4 ± 3.9 ml/min, indicating an increase in TALH reabsorption which was attributed to increased sodium and water reaching this segment. Time control studies showed no significant changes in the parameters measured except for potassium excretion. Potassium excretion during calcium infusion was somewhat lower than during the control studies. The data support the view that an increase in serum calcium concentration leads to a decrease in proximal tubular reabsorption as indicated by lithium clearance while a decrease in reabsorption in the collecting duct could well add to the diuretic properties of calcium.